Expression of VEGFR-2 on HaCaT cells is regulated by VEGF and plays an active role in mediating VEGF induced effects.
Expression of VEGFR-2 on HaCaT cells is regulated by VEGF and plays an active role in mediating VEGF induced effects.
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DOI：
10.1016/j.bbrc.2006.07.213
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发表时间：
2006-10
影响因子：
3.1
通讯作者：
Xiao-hong Yang;X. Man;S. Cai;Yong-Gang Yao;Z. Bu;M. Zheng
中科院分区：
文献类型：
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作者：
Xiao-hong Yang;X. Man;S. Cai;Yong-Gang Yao;Z. Bu;M. Zheng
血管内皮生长因子（VEGF）及其受体VEGFR-2在内皮细胞的有丝分裂和趋化过程中起重要作用。在正常人皮肤中，VEGF由表皮角质形成细胞表达和分泌。新出现的数据表明，角质形成细胞衍生的VEGF靶向除真皮内皮细胞以外的其他细胞类型。我们最近发现，来自人类正常皮肤的角质形成细胞表达所有五种已知的VEGF受体和共受体（神经纤毛蛋白1和2）。为了确定表皮中VEGFR-2的功能意义，我们研究了其在角质形成细胞系HaCaT细胞中对VEGF治疗的反应。在RNA和蛋白质水平上证实了HaCaT细胞上VEGFR-2的表达，并且受VEGF 165处理的调节。VEGF 165处理HaCaT细胞后，VEGFR-2酪氨酸自磷酸化，PLC-γ和p44/42 MAPK磷酸化呈时间依赖性。用VEGFR-2中和抗体（MAB 3571）预孵育完全消除了这些磷酸化作用。此外，VEGF 165刺激HaCaT细胞的增殖和迁移，并且这种作用被MAB 3571预处理显著阻断。在HaCaT细胞中中和VEGFR-2增加了培养期间的细胞粘附。我们的研究结果表明，HaCaT细胞上表达的VEGFR-2在VEGF介导的细胞活性调节中起着至关重要的作用。
Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 play important roles in mitogenesis and chemotaxis of endothelial cells. In normal human skin, VEGF is expressed and secreted by epidermal keratinocytes. Emerging data suggest that keratinocyte-derived VEGF targets other cell types besides the dermal endothelial cells. We have recently showed that keratinocytes from human normal skin expressed all five known VEGF receptors and co-receptors (neuropilin 1 and 2). To define the functional significance of VEGFR-2 in epidermis, we examined its role in a keratinocyte cell line, HaCaT cells, in response to VEGF treatment. Expression of VEGFR-2 on HaCaT cells was confirmed at both RNA and protein levels and was regulated by VEGF165treatment. Treatment of HaCaT cells with VEGF165induced tyrosine-autophosphorylation of VEGFR-2 and phosphorylation of PLC-γ and p44/42 MAPK in a time-dependent manner. Preincubation with a neutralizing antibody for VEGFR-2 (MAB3571) completely abrogated these phosphorylation effects. Furthermore, VEGF165stimulated proliferation and migration of HaCaT cells, and this effect was significantly blocked by a pretreatment with MAB3571. Neutralizing VEGFR-2 in HaCaT cells increased cell adhesion during culture. Our results suggest that VEGFR-2 expressed on HaCaT cells plays a crucial role in VEGF-mediated regulation of cell activity.